Response of mineral particles in inland lakes to water optical properties and its influence on chlorophyll-a estimation.

Many chlorophyll-a (Chl-a) remote sensing estimation algorithms have been developed for inland water, and they are proposed always based on some ideal assumptions, which are difficult to meet in complex inland waters. Based on MIE scattering theory, this study calculated the optical properties of mineral particles under different size distribution and refractive index conditions, and the Hydrolight software was employed to simulate remote sensing reflectance in the presence of different mineral particles. The findings indicated that the reflectance is significantly influenced by the slope (j) of particle size distribution function and the imaginary part (n') of the refractive index, with the real part (n) having a comparatively minor impact. Through both a simulated dataset containing 18,000 entries and an in situ measured dataset encompassing 2183 data from hundreds of lakes worldwide, the sensitivities of band ratio (BR), fluorescence baseline height (FLH), and three-band algorithms (TBA) to mineral particles were explored. It can be found that BR showed the best tolerance to mineral particles, followed by TBA. However, when the ISM concentration is less than 30 g m-3, the influence of CDOM cannot be ignored. Additionally, a dataset of over 400 entries is necessary for developing the BR algorithm to mitigate the incidental errors arising from differences in data magnitude. And if the amount of developing datasets is less than 400 but greater than 200, the TBA algorithm is more likely to obtain more stable accuracy.

Applied Research of Case-based Learning Teaching in Nephrology Medicine for Professional Postgraduate Students in Clinical Medicine.

Objective: To explore the influence of case-based learning (CBL) teaching methods in comparison to the traditional lecture-based learning (LBL) model in clinical teaching of nephrology for master's degree students in clinical medicine. Methods: Clinical medicine master's degree students who were trained in the Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University from December 2015 to December 2021 were selected as the study objects. The selected students were divided into two groups: the LBL group comprised 16 graduate students who received the traditional LBL model from December 2015 to December 2018, and the CBL group comprised 18 graduate students who received the CBL teaching methods from January 2019 to December 2021. Both groups participated in the professional theoretical knowledge assessment, including objective and subjective questions and calculating the total score), and the examination of clinical skills communication ability, preparation of handling materials, anesthesia techniques, operational skills, aseptic techniques, and postoperative management), at the time of discharge from the department. The independent learning ability (self-management ability, information ability, and learning ability) of students of the two groups after teaching was then assessed, and the satisfaction of the two groups with their respective teaching mode (including satisfaction with the teaching format, teaching effectiveness, interest stimulation, independent learning and the improvement of teamwork ability) was assessed by the questionnaire on the degree of satisfaction of the two groups. Results: The assessment scores of professional theoretical knowledge in the CBL group were significantly higher than those in the LBL group in objective questions, subjective questions, and total scores (P1 = .028; P2 = .036; P3 = .041). The CBL group scored higher than the LBL group in the assessment of communication skills, preparation of operative items, anesthesia technique, operative skills, aseptic technique, and postoperative handling skills, but the differences were not statistically significant (P1 = .071; P2 = .260; P3 = .184; P4 = .127; P5 = .352; P6 = .584). The self-management ability, information ability, and learning ability scores of students in the CBL group were significantly higher than those in the LBL group (P1 = .006; P2 = .013; P3 = .003). Students in the CBL group were significantly higher than those in the LBL group in terms of satisfaction with teaching form, teaching effect, interest stimulation, improvement of independent learning ability, and satisfaction with teamwork ability (P1 = .015; P2 = .008; P3 = .010; P4 = .024; P5 = .022). Conclusions: The CBL teaching model can improve and enhance the clinical thinking ability of clinical medicine master's degree students in nephrology, and stimulate their interest in learning. Professional master's degree students have a high degree of satisfaction with the CBL model.

Gastrointestinal symptoms of long COVID-19 related to the ectopic colonization of specific bacteria that move between the upper and lower alimentary tract and alterations in serum metabolites.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) outbreak, many COVID-19 variants have emerged, causing several waves of pandemics and many infections. Long COVID-19, or long-term sequelae after recovery from COVID-19, has aroused worldwide concern because it reduces patient quality of life after rehabilitation. We aimed to characterize the functional differential profile of the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. METHODS: We prospectively collected oral, fecal, and serum samples from 983 antibiotic-naïve patients with mild COVID-19 and performed a 3-month follow-up postdischarge. Forty-five fecal and saliva samples, and 25 paired serum samples were collected from patients with gastrointestinal symptoms of long COVID-19 at follow-up and from healthy controls, respectively. Eight fecal and saliva samples were collected without gastrointestinal symptoms of long COVID-19 at follow-up. Shotgun metagenomic sequencing of fecal samples and 2bRAD-M sequencing of saliva samples were performed on these paired samples. Two published COVID-19 gut microbiota cohorts were analyzed for comparison. Paired serum samples were analyzed using widely targeted metabolomics. RESULTS: Mild COVID-19 patients without gastrointestinal symptoms of long COVID-19 showed little difference in the gut and oral microbiota during hospitalization and at follow-up from healthy controls. The baseline and 3-month samples collected from patients with gastrointestinal symptoms associated with long COVID-19 showed significant differences, and ectopic colonization of the oral cavity by gut microbes including 27 common differentially abundant genera in the Proteobacteria phylum, was observed at the 3-month timepoint. Some of these bacteria, including Neisseria, Lautropia, and Agrobacterium, were highly related to differentially expressed serum metabolites with potential toxicity, such as 4-chlorophenylacetic acid, 5-sulfoxymethylfurfural, and estradiol valerate. CONCLUSIONS: Our study characterized the changes in and correlations between the oral and gut microbiomes and serum metabolites in patients with gastrointestinal symptoms associated with long COVID-19. Additionally, our findings reveal that ectopically colonized bacteria from the gut to the oral cavity could exist in long COVID-19 patients with gastrointestinal symptoms, with a strong correlation to some potential harmful metabolites in serum.

Hydrogels as dynamic memory with forgetting ability.

The memory of our brain, stored in soft matter, is dynamic, and it forgets spontaneously to filter unimportant information. By contrast, the existing manmade memory, made from hard materials, is static, and it does not forget without external stimuli. Here we propose a principle for developing dynamic memory from soft hydrogels with temperature-sensitive dynamic bonds. The memorizing-forgetting behavior is achieved based on fast water uptake and slow water release upon thermal stimulus, as well as thermal-history-dependent transparency change of these gels. The forgetting time is proportional to the thermal learning time, in analogy to the behavior of brain. The memory is stable against temperature fluctuation and large stretching; moreover, the forgetting process is programmable. This principle may inspire future research on dynamic memory based on the nonequilibrium process of soft matter.

Dual-Responsive Curcumin-Loaded Nanoparticles for the Treatment of Cisplatin-Induced Acute Kidney Injury.

Acute kidney injury (AKI) has been a global public health concern leading to high patient morbidity and mortality in the world. Nanotechnology-mediated antioxidative therapy has facilitated the treatment of AKI. Herein, a hierarchical curcumin-loaded nanodrug delivery system (NPS@Cur) was fabricated for antioxidant therapy to ameliorate AKI. The nanoplatform could respond to subacidic and reactive oxygen species (ROS) microenvironments. The subacidic microenvironment led to a smaller size (from 140.9 to 99.36 nm) and positive charge (from -4.9 to 12.6 mV), contributing to the high accumulation of nanoparticles. An excessive ROS microenvironment led to nanoparticle degradation and drug release. In vitro assays showed that NPS@Cur could scavenge excessive ROS and relieve oxidative stress in H2O2-induced HK-2 cells through reduced apoptosis, activated autophagy, and decreased endoplasmic reticulum stress. Results from cisplatin-induced AKI models revealed that NPS@Cur could effectively alleviate mitochondria injury and protect kidneys via antioxidative protection, activated autophagy, decreased endoplasmic reticulum stress, and reduced apoptosis. NPS@Cur showed excellent biocompatibility and low toxicity to primary tissues in mice. These results revealed that NPS@Cur may be a potential therapeutic strategy for efficiently treating cisplatin or other cause-induced AKI.

Quantitative determination of cation-π interactions between metal ions and aromatic groups in aqueous media by a hydrogel Donnan potential method.

Cation-π interactions in aqueous media are known to play critical roles in various biological activities. However, quantitative experimental information, such as the binding ratio of metal ions to aromatic groups, is hardly available due to the lack of a suitable test system and method. Herein, we proposed a hydrogel Donnan potential method to determine the binding ratio of metal ions to aromatic groups on polymer networks in aqueous media. In this method, we adopted recently developed poly(cation-π) hydrogels with a rich adjacent sequence of the cationic group and the aromatic group on the polymer network. A microelectrode technique (MET) is used to measure the Donnan potential of the poly(cation-π) hydrogels. From the Donnan potential, the binding ratios of various metal ions to aromatic groups are quantitatively determined for the first time.

Temporary Trend, Characteristics and Clinical Outcomes of Acute Pancreatitis Patients Infected with Human Immunodeficiency Virus.

BACKGROUND: Compared to general population, human immunodeficiency virus (HIV) infection may increase frequency of acute pancreatitis (AP); however, evidence regarding effects of HIV infection on AP-related outcomes is limited and controversial. AIMS: We aim to investigate the temporary trend, characteristics and clinical outcomes of AP infected with HIV. METHODS: We reviewed data from the 2003-2014 National Inpatient Sample to identify patients with a primary diagnosis of AP. The primary outcomes (in-hospital mortality, acute respiratory failure, acute kidney injury, and prolonged length of stay [LOS]) and secondary outcomes (gastrointestinal hemorrhage, sepsis and total cost) were compared between patients with and without HIV infection using univariate, multivariable and propensity score matching analyses. RESULTS: Of 594,106 patients diagnosed with AP, 6775 (1.14%) had HIV infection. Patients with HIV were more likely to be younger, black, male, less likely to be gallstone-related and had lower rate of interventions. Multivariable analyses based on multiple imputation revealed that HIV infection was associated with higher risk of mortality (odds ratio [OR]: 1.74; 95% confidence interval [CI] 1.34-2.25), acute kidney injury (OR: 1.13; 95% CI 1.19-1.44), prolonged LOS (OR: 1.26; 95% CI 1.15-1.37) and 6% higher cost. There were no differences in sepsis, gastrointestinal bleeding, and respiratory failure between groups. CONCLUSIONS: HIV infection is associated with adverse outcomes including increased mortality, acute kidney injury and more healthcare utilization in AP patients. More assertive management strategies like early intravenous fluid resuscitation in HIV patients hospitalized with AP to prevent acute kidney injury may be helpful to improve clinical outcomes.

Autophagosome protects proximal tubular cells from aldosterone-induced senescence through improving oxidative stress.

Aldosterone exerts an enormous function on proximal tubular cells (PTC) senescence, which is a common pathomechanism contributing to renal dysfunction. Numerous studies have shown that oxidative stress is deeply involved in the pathophysiologic processes of chronic kidney diseases. The study aims to investigate whether autophagy could regulate the process of senescence through oxidative stress in PTC both in vivo and ex vivo. Our results suggested that aldosterone treatment increased the senescence and oxidative stress as evidenced by increased percent of SA-ß-Gal positive cells, reactive oxygen species level, expression of NADPH oxidase 4 (NOX4) rather than NOX2, and the up-regulation of p21 in cultured PTC. Furthermore, the alternation of the expression of p62 and LC3-II/LC3-I demonstrated that aldosterone treatment remarkably influenced autophagic flux. NOX4 siRNA treatment or autophagy induction with rapamycin reduced the oxidative stress and senescence in aldosterone-induced PTC. On the contrary, inhibition of autophagy with chloroquine worsened these changes. Similar results were further confirmed in vivo. Our results suggested that autophagy may become a realistic therapeutic strategy against aldosterone-induced PTC injury via improving oxidative stress.

Isoliquiritigenin ameliorates caerulein-induced chronic pancreatitis by inhibiting the activation of PSCs and pancreatic infiltration of macrophages.

Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone-type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein-induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF-κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti-inflammatory and anti-fibrotic therapeutic agent for CP.

Atrial fibrillation in hospitalized patients with end-stage liver disease: temporal trends in prevalence and outcomes.

BACKGROUND & AIMS: End-stage liver disease (ESLD) happens due to the development and progression of chronic liver disease. This study aims to investigate the temporal trend, patient characteristics and outcomes of atrial fibrillation (AF) in hospitalized ESLD patients across the United States. METHODS: Nationwide Inpatient Sample from 2003 to 2014 was utilized to retrospectively study the weighted prevalence of AF in hospitalized ESLD patients. Multivariable regression models were used to assess the association between AF with clinical factors, in-hospital mortality, length of stay (LOS) and cost. RESULTS: 639 345 hospitalizations associated with ESLD were identified, of which 47 710 (7.48%) were diagnosed with AF. The prevalence of AF increased from 5.73% in 2003 to 9.75% in 2014 in ESLD and varied by age, race, income, insurance type and hospital characteristics. Factors associated with AF included advancing age, male, white race, high income and urban teaching hospital. AF presence was associated with significant higher in-hospital mortality (odds ratio, 1.40; 95% confidence interval, 1.35-1.45), 21% longer LOS and 22% higher cost. In addition, a significant decreasing trend in in-hospital mortality was observed (from 16.70% to 10.63% in patients with AF and from 10.74% to 7.50% in patients without AF). CONCLUSIONS: The prevalence of AF in hospitalized ESLD patients has continued to increase from 2003 through 2014. AF is associated with poor prognosis and higher health resource utilization. Innovative anticoagulation strategies through improved collaboration between cardiologists and hepatologists are required for better management of hospitalized ESLD patients comorbid with AF.

Surface charge dominated protein absorption on hydrogels.

Soft tissue engineering requires antifouling materials that are biocompatible and mechanically flexible. Conventional hydrogels containing more than 70 wt% water are thus promising antifouling material candidates. However, some hydrogels are difficult to apply in internal body organs because of undesirable protein absorption on their surfaces. Due to the lack of an effective method for observing the true charge densities of hydrogels, the reason why electrostatic interactions dominate protein absorption behavior remains unclear. In this work, we adopt the microelectrode technique (MET) to study the electrical potentials of hydrogels with negative, positive, and neutral potentials and demonstrate the protein absorption behaviors on those hydrogels. The results show that MET is an effective method to obtain the surface charge densities of various hydrogels. Furthermore, the amounts of absorbed proteins on the gels were quantified with respect to the charge densities of the hydrogels. The results indicate that electrostatic absorption is quantitatively dominated by a combination of hydrogel charge density and overall protein charge. Based on the knowledge obtained in this work, the effects of hydrogel surface charges on protein absorption can be better understood. Thus, the results are expected to promote the application of hydrogels in tissue engineering.

Risk factors and nomogram for diabetes mellitus in idiopathic chronic pancreatitis.

BACKGROUND AND AIM: Diabetes mellitus (DM) is a common complication of idiopathic chronic pancreatitis (ICP), which impairs the quality of life for patients. This study aimed to identify risk factors and develop nomogram for DM in ICP to help early diagnosis. METHODS: Idiopathic chronic pancreatitis patients admitted to our center from January 2000 to December 2013 were included. Cumulative rates of DM were calculated by Kaplan-Meier method. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on training cohort, risk factors for DM were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: Totally, 1633 patients with ICP were finally enrolled. The median follow-up duration was 9.8 years. DM was found in 26.3% (430/1633) of patients after the onset of CP. Adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct were identified risk factors for DM development. The nomogram achieved good concordance indexes in the training and validation cohorts, respectively, with well-fitted calibration curves. CONCLUSIONS: Risk factors were identified, and nomogram was developed to determine the risk of DM in ICP patients. Patients with one or more of the risk factors including adult at onset of ICP, biliary stricture at/before diagnosis of CP, steatorrhea at/before diagnosis of CP, and complex pathologic changes in main pancreatic duct have higher incidence of DM.

Risk Factors and Nomogram for Pancreatic Stone Formation in Chronic Pancreatitis over a Long-Term Course: A Cohort of 2,153 Patients.

BACKGROUND: Pancreatic stones are pathognomonic of chronic pancreatitis (CP). This study aimed to determine the incidence, identify risk factors, and develop a nomogram for pancreatic stones in CP patients. METHODS: Patients with CP admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic stones after the onset of CP and after the diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2,153 CP patients, pancreatic stones were detected in 1,626 (75.5%) patients, with a median follow-up of 7.8 years. Age at the onset of CP, body mass index, smoking, diabetes mellitus, pancreatic pseudocyst, biliary stricture, severe acute pancreatitis, and type of pain were identified risk factors for pancreatic stones development. The nomogram with these 8 factors achieved good accuracy. CONCLUSIONS: The nomogram achieved an individualized prediction of pancreatic stones development in CP. It may help the management of pancreatic stones.

Dasatinib ameliorates chronic pancreatitis induced by caerulein via anti-fibrotic and anti-inflammatory mechanism.

Chronic pancreatitis (CP) is characterized by persistent inflammation and fibrosis of the pancreas. To date, no clinical therapy is available to reverse the inflammatory damage or pancreatic fibrosis associated with CP. This study systematically investigated the effect of Dasatinib, a multiple tyrosine kinases (TKs) inhibitor, on pancreatic fibrosis and inflammation in vivo and in vitro. We found that Dasatinib notably ameliorated pancreatic fibrosis and infiltration of macrophages in a model of caerulein-induced murine CP. Further RNA-seq and phosphoproteomic analysis and in vitro validation assays indicated that Dasatinib exerted a marked inhibition on the proliferation and activation of PSCs, which may be resulted from increased GSK3ß-mediated ß-catenin cytosol retention by inhibiting upstream multiple TKs (such as PDGFR and Src) and MAPK cascades (including ERK1/2 and p38 MAPK). In addition, Dasatinib significantly restrained both the M1 and M2 polarization of macrophages, and impeded its recruitment and crosstalk with PSCs. Our findings indicated that Dasatinib is a potential anti-inflammatory and anti-fibrotic therapeutic strategy for CP.

Risk Factors and Nomogram for Common Bile Duct Stricture in Chronic Pancreatitis: A Cohort of 2153 Patients.

GOALS: To identify the risk factors and develop nomograms for common bile duct (CBD) stricture in chronic pancreatitis (CP) patients. BACKGROUND: CBD stricture is a common complication in CP and has a variable clinical presentation ranging from asymptomatic to overt jaundice and cholangitis. STUDY: Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of CBD stricture after onset and diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. On the basis of the training cohort, risk factors for CBD stricture and symptomatic CBD stricture were identified through Cox proportional hazards regression model, and nomograms was developed, respectively. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2153 patients, the median duration of follow-up was 7.0 years. CBD strictures were detected in 340 (15.8%) patients, whereas 159 of them were symptomatic. Male gender, age at onset of CP, smoking, body mass index, and morphology of main pancreatic duct were identified risk factors for CBD stricture development. Age at onset of CP, body mass index, and type of pain were identified risk factors for symptomatic CBD stricture development. Both nomograms achieved good concordance indexes with well-fitted calibration curves. CONCLUSIONS: The nomogram achieved an individualized prediction of symptomatic CBD stricture development in CP patients. It may help the early diagnosis and intervention of symptomatic CBD stricture and reduce the rates of severe adverse events.

Autoantibody detection is not recommended for chronic pancreatitis: a cross-sectional Study of 557 patients.

BACKGROUND: Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown. METHODS: Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis. RESULTS: In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-ß2-glycoprotein I (ß2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum ß2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P < 0.05). Multivariate logistic regression analysis result showed that diabetes mellitus (OR = 2.515) and common bile duct stricture (OR = 2.844) were the risk factors of positive ß2-GPI antibody in patients while diabetes mellitus in first-/second-/third-degree relatives (OR = 0.266) was the protective factor. There were no related factors for other three differentially expressed autoantibodies. CONCLUSIONS: Four autoantibodies were expressed differentially between patients with non-AIP CP and historial healthy controls. Due to limited significance for diagnosis and treatment of chronic pancreatitis, autoantibodies detection is not recommended conventionally unless suspected of AIP.

Extracorporeal shock wave lithotripsy is safe and effective for geriatric patients with chronic pancreatitis.

BACKGROUND AND AIM: Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is a first-line treatment for chronic pancreatitis (CP) patients with pancreatic stones. However, the performance of P-EWSL in geriatric patients remains unclear. We aimed to evaluate the safety and efficacy of P-ESWL for them. METHODS: This prospective study was conducted in painful CP patients who underwent P-ESWL. Patients aged over 65 years were included in geriatric group; patients aged under 65 years were assigned to control group. For the long-term follow-up investigation, geriatric patients were matched with patients from the control group in a 1:1 ratio. Primary outcomes were complications of P-ESWL and pain relief. Secondary outcomes included stone clearance, physical and mental health, quality of life score, changes in exocrine and endocrine pancreatic function, and survival. RESULTS: From March 2011 to March 2016, P-ESWL was performed in 1404 patients (72 in the geriatric group and 1332 in the control group). No significant differences were observed in complications of P-ESWL between the two groups (P = 0.364). Among the 67 (67/72, 93.1%) geriatric patients who underwent follow up for 4.02 years, complete pain relief was achieved in 53 patients, which was not significantly different from that of matched controls (54/70; P = 0.920). The death in the geriatrics was significantly higher (P = 0.007), but none of them were correlated with P-ESWL. CONCLUSIONS: P-ESWL is safe and effective for geriatric CP patients with pancreatic stones. It can promote significant pain relief and stone clearance and improve quality of life and mental and physical health.

Glucagon-like peptide-1 analog prevents obesity-related glomerulopathy by inhibiting excessive autophagy in podocytes.

To investigate the role of glucagon-like peptide-1 analog (GLP-1) in high-fat diet-induced obesity-related glomerulopathy (ORG). Male C57BL/6 mice fed a high-fat diet for 12 wk were treated with GLP-1 (200 µg/kg) or 0.9% saline for 4 wk. Fasting blood glucose and insulin and the expression of podocin, nephrin, phosphoinositide 3-kinase (PI3K), glucose transporter type (Glut4), and microtubule-associated protein 1A/1B-light chain 3 (LC3) were assayed. Glomerular morphology and podocyte foot structure were evaluated by periodic acid-Schiff staining and electron microscopy. Podocytes were treated with 150 nM GLP-1 and incubated with 400 µM palmitic acid (PA) for 12 h. The effect on autophagy was assessed by podocyte-specific Glut4 siRNA. Insulin resistance and autophagy were assayed by immunofluorescence and Western blotting. The high-fat diet resulted in weight gain, ectopic glomerular lipid accumulation, increased insulin resistance, and fusion of podophyte foot processes. The decreased translocation of Glut4 to the plasma membrane and excess autophagy seen in mice fed a high-fat diet and in PA-treated cultured podocytes were attenuated by GLP-1. Podocyte-specific Glut4 siRNA promoted autophagy, and rapamycin-enhanced autophagy worsened the podocyte injury caused by PA. Excess autophagy in podocytes was induced by inhibition of Glut4 translocation to the plasma membrane and was involved in the pathology of ORG. GLP-1 restored insulin sensitivity and ameliorated renal injury by decreasing the level of autophagy.

Risk factor for steatorrhea in pediatric chronic pancreatitis patients.

BACKGROUND: Pediatric patients always suffer from chronic pancreatitis (CP), especially those with steatorrhea. This study aimed to identify the incidence of and risk factors for steatorrhea in pediatric CP. To our best knowledge, there is no pediatric study to document the natural history of steatorrhea in CP. METHODS: CP patients admitted to our center from January 2000 to December 2013 were enrolled. Patients were assigned to the pediatric (< 18 years old) and adult group according to their age at onset of CP. Cumulative rates of steatorrhea in both groups were calculated. Risk factors for both groups were identified, respectively. RESULTS: The median follow-up duration for the whole cohort was 7.6 years. In a total of 2153 patients, 13.5% of them were pediatrics. The mean age at the onset and the diagnosis of CP in pediatrics were 11.622 and 19.727, respectively. Steatorrhea was detected in 46 patients (46/291, 15.8%) in the pediatric group and in 447 patients (447/1862, 24.0%) in the adult group. Age at the onset of CP (hazard ratio [HR], 1.121), diabetes mellitus (DM, HR, 51.140), and severe acute pancreatitis (SAP, HR, 13.946) was identified risk factor for steatorrhea in the pediatric group. CONCLUSIONS: Age at the onset of CP, DM and SAP were identified risk factors for the development of steatorrhea in pediatric CP patients. The high-risk populations were suggested to be followed up closely. They may benefit from a full adequate pancreatic exocrine replacement therapy.

Apoptosis-Associated Speck-Like Protein Containing a CARD Deletion Ameliorates Unilateral Ureteral Obstruction Induced Renal Fibrosis and Endoplasmic Reticulum Stress in Mice.

Inflammation might be one of the essential underlying mechanisms of renal fibrosis, which is considered a key pathological feature of end-stage renal disease and is closely associated with proteinuria and decreased renal function. Apoptosis-associated speck-like protein containing a CARD (ASC), identified as the central structure of inflammasome, is involved in the progression of interstitial fibrosis; however, its signal transduction pathways remain unclear. In the present study, we performed unilateral ureter obstruction (UUO) in both wild-type and ASC deletion mice to determine the contribution of ASC to renal fibrosis. Compared with control groups, UUO significantly induced renal fibrosis and collagen deposition, as evidenced by photomicrographs. ASC deletion attenuated renal injury, reduced cell infiltration and the release of inflammatory cytokines, protected against apoptosis, and downregulated the PRKR-like endoplasmic reticulum kinase (PERK) pathway of endoplasmic reticulum (ER) stress. Our data identify a novel role of ASC in the regulation of renal fibrosis and ER stress after UUO, strongly indicating that ASC could serve as an attractive target in the treatment of chronic kidney disease.